Silver diamine fluoride for managing carious lesions:an umbrella review

Background: This umbrella review comprehensively appraised evidence for silver diamine fluoride (SDF) to arrest and prevent root and coronal caries by summarizing systematic reviews. Adverse events were explored. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, PubMed, Embase, Cochrane Library, PROSPERO register and Joanna Briggs Institute Database of Systematic Reviews were searched for systematic reviews investigating SDF for caries prevention or arrest (1970–2018) without language restrictions. Systematic reviews were selected, data extracted, and risk of bias assessed using ROBIS by two independent reviewers, in duplicate. Corrected covered area was calculated to quantify studies’ overlap across reviews. Results: Eleven systematic reviews were included; four focussing on SDF for root caries in adults and seven on coronal caries in children. These cited 30 studies (4 root caries; 26 coronal caries) appearing 63 times. Five systematic reviews were of “low”, one“unclear” and five “high” risk of bias. Overlap of studies was very high (50% root caries; 17% coronal caries). High overlap and heterogeneity, mainly comparators and outcome measures, precluded meta-analysis. Results were grouped by aim and outcomes to present an overview of direction and magnitude of effect. SDF had a positive effect on prevention and arrest of coronal and root caries, consistently outperforming comparators (fluoride varnish, Atraumatic Restorative Treatment, placebo). For root caries prevention, the prevented fraction (PF) was 25–71% higher for SDF compared to placebo (two systematic reviews with three studies) and PF=100–725% for root caries arrest (one systematic review with two studies). For coronal caries prevention, PF=70–78% (two systematic reviews with two studies) and PF=55–96% for coronal caries arrest (one systematic review with two studies) with arrest rates of 65–91% (four systematic reviews with six studies). Eight systematic reviews reported adverse events, seven of which reported arrested lesions black staining. Conclusion: Systematic reviews consistently supported SDF’s effectiveness for arresting coronal caries in the primary dentition and arresting and preventing root caries in older adults for all comparators. There is insufficient evidence to draw conclusions on SDF for prevention in primary teeth and prevention and arrest in permanent teeth in children. No serious adverse events were reported

Collaborative Musical Expression and Creativity Among Academics: When Intellectualism Meets Twelve Bar Blues

The Professors are a blues, rock, and sometime heavy metal band made up of communication professors from a number of New Jersey schools. Formed in 1995, the band has played in clubs in New York City as well as a number of academic venues, including the annual conference of the International Communication Association in Chicago in 1996 and the annual conference of the National Communication Association in New York City in 1998. The Professors have been featured in both local and national press, including the Chronicle of Higher Education. When we learned of the call for papers for this special issue of the American Communication Journal addressing the creative endeavors of Communication scholars beyond their regular research agendas, we were delighted to have the opportunity to reflect upon the place of musical creativity within our lives as working academics. What follows in this paper are the thoughts of a number of band members, past and present, who trace the relationship of the musical, the creative, and the intellectual in terms of their own personal histories and academic interests

Topical silver diamine fluoride for managing dental caries in children and adults

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of silver diamine fluoride in arresting and preventing caries in deciduous and permanent teeth (coronal and root caries) compared to any other intervention including placebo or no treatment.</p

An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations.

Parietal cortex RNA-sequencing (RNA-seq) data were generated from individuals with and without Alzheimer disease (AD; ncontrol = 13; nAD = 83) from the Knight Alzheimer Disease Research Center (Knight ADRC). Using this and an independent (Mount Sinai Brain Bank (MSBB)) AD RNA-seq dataset, cortical circular RNA (circRNA) expression was quantified in the context of AD. Significant associations were identified between circRNA expression and AD diagnosis, clinical dementia severity and neuropathological severity. It was demonstrated that most circRNA-AD associations are independent of changes in cognate linear messenger RNA expression or estimated brain cell-type proportions. Evidence was provided for circRNA expression changes occurring early in presymptomatic AD and in autosomal dominant AD. It was also observed that AD-associated circRNAs co-expressed with known AD genes. Finally, potential microRNA-binding sites were identified in AD-associated circRNAs for miRNAs predicted to target AD genes. Together, these results highlight the importance of analyzing non-linear RNAs and support future studies exploring the potential roles of circRNAs in AD pathogenesis

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio

Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study

The SCHOLAR-5 study examines treatment patterns and outcomes of real-world follicular lymphoma (FL) patients on 3rd line of treatment (LoT) or higher, for whom existing data are limited. SCHOLAR-5 is a retrospective cohort study using data from adults (≥ 18 years) with grade 1-3a FL, initiating ≥3rd LoT after June 2014 at major lymphoma centers in the United States (US) and Europe. Objective response rate (ORR), complete response (CR), progression free survival (PFS) and overall survival (OS) were analyzed by LoT. Time-to-event outcomes were assessed using Kaplan-Meier methods. Of 128 patients, 87 initiated 3rd LoT, 63 initiated 4th LoT, and 47 initiated 5th LoT. At 1st eligible LoT, 31% progressed within 24-months of 1st LoT anti-CD20 combination therapy, 28% had prior autologous stem-cell transplantation, and 31% were refractory to the previous LoT. The most common regimen in each LoT was chemoimmunotherapy; however, experimental drugs were increasingly used at later LoTs. In the US, anti-CD20 monotherapy was more common at ≥3rd LoT compared to Europe, where stem cell transplants were more common. ORR at 3rd LoT was 68% (CR 44%), but decreased after each LoT to 37% (CR 22%) in ≥5 LoT. Median OS and PFS at 3rd LoT were 68 and 11 months, respectively, and reduced to 43 and 4 months at ≥5 LoT. Treatments were heterogenous at each LoT in both the US and Europe. Few FL patients achieved complete response in later LoT, and duration of response and survival diminished with each subsequent line

Cerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers.

Clinical and neuropathological characteristics associated with G4C2 repeat expansions in chromosome 9 open reading frame 72 (C9ORF72), the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, are highly variable. To gain insight on the molecular basis for the heterogeneity among C9ORF72 mutation carriers, we evaluated associations between features of disease and levels of two abundantly expressed "c9RAN proteins" produced by repeat-associated non-ATG (RAN) translation of the expanded repeat. For these studies, we took a departure from traditional immunohistochemical approaches and instead employed immunoassays to quantitatively measure poly(GP) and poly(GA) levels in cerebellum, frontal cortex, motor cortex, and/or hippocampus from 55 C9ORF72 mutation carriers [12 patients with ALS, 24 with frontotemporal lobar degeneration (FTLD) and 19 with FTLD with motor neuron disease (FTLD-MND)]. We additionally investigated associations between levels of poly(GP) or poly(GA) and cognitive impairment in 15 C9ORF72 ALS patients for whom neuropsychological data were available. Among the neuroanatomical regions investigated, poly(GP) levels were highest in the cerebellum. In this same region, associations between poly(GP) and both neuropathological and clinical features were detected. Specifically, cerebellar poly(GP) levels were significantly lower in patients with ALS compared to patients with FTLD or FTLD-MND. Furthermore, cerebellar poly(GP) associated with cognitive score in our cohort of 15 patients. In the cerebellum, poly(GA) levels similarly trended lower in the ALS subgroup compared to FTLD or FTLD-MND subgroups, but no association between cerebellar poly(GA) and cognitive score was detected. Both cerebellar poly(GP) and poly(GA) associated with C9ORF72 variant 3 mRNA expression, but not variant 1 expression, repeat size, disease onset, or survival after onset. Overall, these data indicate that cerebellar abnormalities, as evidenced by poly(GP) accumulation, associate with neuropathological and clinical phenotypes, in particular cognitive impairment, of C9ORF72 mutation carriers

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1